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BACKGROUND Antibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention. AIM To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen. METHODS We included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen. RESULTS Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001). CONCLUSION The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.

Background The drug resistance rate of clinical Helicobacter pylori (H. pylori) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. Aim To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. Methods Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. Results The strains showing a high degree of homology with hp26695, hp1181, and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. Conclusion Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.

Background Advances in endoscopic imaging enable the identification of patients at high risk of gastric cancer. However, there are no comparative data on the utility of standard and magnifying narrow-band imaging (M-NBI) endoscopy for diagnosing Helicobacter pylori (H. pylori) infection, gastric atrophy, and intestinal metaplasia. Aim To compare the diagnostic performance of standard and M-NBI endoscopy for H. pylori gastritis and precancerous conditions. Methods In 254 patients, standard endoscopy findings were classified into mosaic-like appearance (type A), diffuse homogenous redness (type B), and irregular redness with groove (type C). Gastric mucosal patterns visualized by M-NBI were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), and loss of gastric pits with coiled vessels (type Z-3). Results The diagnostic accuracy of standard and M-NBI endoscopy for H. pylori gastritis was 93.3% and 96.1%, respectively. Regarding gastric precancerous conditions, the accuracy of standard and M-NBI endoscopy was 72.0% vs 72.6% for moderate to severe atrophy, and 61.7% vs. 61.1% for intestinal metaplasia in the corpus, respectively. Compared to type A and Z-1, types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy [odds ratio (OR) = 5.56 and 8.67] and serum pepsinogen I/II ratio of ≤ 3 (OR = 4.48 and 5.69). Conclusion Close observation of the gastric mucosa by standard and M-NBI endoscopy is useful for the diagnosis of H. pylori gastritis and precancerous conditions.

Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative, human gastric pathogen found usually in the mucous lining of stomach. It infects more than 50% of the world’s population and leads to gastroduodenal diseases. The outcome of disease depends on mainly three factors: Host genetics, environment and bacterial factors. Among these, bacterial virulence factors such as cagA, vacA are well known for their role in disease outcomes. However, based on the global epidemiological results, none of the bacterial virulence (gene) factors was found to be associated with particular diseases like duodenal ulcer (DU) in all populations. Hence, substantial importance has been provided for research in strain-specific genes outside the cag pathogenicity island, especially genes located within the plasticity regions. dupA found within the plasticity regions was first demonstrated in 2005 and was proposed for duodenal ulcer development and reduced risk of gastric cancer in certain geographical regions. Due to the discrepancies in report from different parts of the world in DU development related to H. pylori virulence factor, dupA became an interesting area of research in elucidating the role of this gene in the disease progression. In this review, we shed light on the detailed information available on the polymorphisms in dupA and their clinical relevance. We have critically appraised several pertinent studies on dupA and discussed their merits and shortcomings. This review also highlights dupA gene as an important biomarker for DU in certain populations.

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa. Today, endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori (H. pylori) infection and evaluate gastric cancer risk. In 2013, the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification, a new grading system for endoscopic gastritis. The Kyoto classification organized endoscopic findings related to H. pylori infection. The Kyoto classification score is the sum of scores for five endoscopic findings (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness with or without regular arrangement of collecting venules) and ranges from 0 to 8. Atrophy, intestinal metaplasia, enlarged folds, and nodularity contribute to gastric cancer risk. Diffuse redness and regular arrangement of collecting venules are related to H. pylori infection status. In subjects without a history of H. pylori eradication, the infection rates in those with Kyoto scores of 0, 1, and ≥ 2 were 1.5%, 45%, and 82%, respectively. A Kyoto classification score of 0 indicates no H. pylori infection. A Kyoto classification score of 2 or more indicates H. pylori infection. Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8, respectively. A Kyoto classification score of 4 or more might indicate gastric cancer risk.

Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.

Background Irritable bowel syndrome (IBS) is a prevalent and debilitating gastrointestinal condition. Research has reported persistent, low-grade mucosal inflammation and significant overlaps between patients with IBS and those with dyspepsia, suggesting a possible pathogenic role of Helicobacter pylori (H. pylori) in IBS. This study therefore aimed to provide the first systematic review and meta-analysis on the association between H. pylori infection and IBS. Aim To investigate the association between H. pylori infection and IBS. Methods Using the keywords "H. pylori OR Helicobacter OR Helicobacter pylori OR infection" AND "irritable bowel syndrome OR IBS", a preliminary search of PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Web of Science, Google Scholar and WanFang databases yielded 2924 papers published in English between 1 January 1960 and 1 June 2018. Attempts were also made to search grey literature. Results A total of 13 clinical studies were systematically reviewed and nine studies were included in the final meta-analysis. Random-effects meta-analysis found a slight increased likelihood of H. pylori infection in patients with IBS, albeit this was not statistically significant (pooled odds ratio 1.47, 95% confidence interval: 0.90-2.40, P = 0.123). It must also be acknowledged that all of the available studies reported only crude odd ratios. H. pylori eradication therapy also does not appear to improve IBS symptoms. Although publication bias was not observed in the funnel plot, there was a high degree of heterogeneity amongst the studies included in the meta-analysis (I 2 = 87.38%). Conclusion Overall, current evidence does not support an association between IBS and H. pylori infection. Further rigorous and detailed studies with larger sample sizes and after H. pylori eradication therapy are warranted.

The survival and replication cycle of Helicobacter pylori (H. pylori) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.

Proton pump inhibitors (PPIs) are one of the most frequently used medications for upper gastrointestinal diseases. However, a number of physicians have raised concern about the serious side effects of long-term use of PPIs, including the development of gastric cancer. Recent epidemiological studies have reported a significant association between long-term PPI intake and the risk of gastric cancer, even after successful Helicobacter pylori eradication. However, the effects of PPIs on the development of pre-malignant conditions such as atrophic gastritis or intestinal metaplasia are not fully known, suggesting the need for comprehensive and confirmative studies are needed in the future. Meanwhile, several experimental studies have demonstrated the effects of PPIs in reducing chemoresistance in gastric cancer cells by modulating the acidic microenvironment, cancer stemness and signal transducer and activator of transcription 3 (STAT3) signaling pathway. The inhibitory effects of PPIs on STAT3 activity may overcome drug resistance and enhance the efficacy of conventional or targeted chemotherapeutic agents. Taken together, PPIs may “play dual role” in gastric carcinogenesis and treatment of gastric cancer.

Helicobacter pylori (H. pylori) antimicrobial resistance is an urgent, global issue. In 2017, the World Health Organization designated clarithromycin-resistant H. pylori as a high priority bacterium for antibiotic research and development. In addition to clarithromycin, resistance to metronidazole and fluoroquinolones has also increased worldwide. Recent international guidelines for management of H. pylori infection recommend bismuth or non-bismuth quadruple therapy for 14 d as a first-line treatment for H. pylori in areas of high clarithromycin and/or metronidazole resistance. Although these treatment regimens provide acceptable H. pylori eradication rates, the regimens used should not contribute to future resistance of H. pylori to antimicrobials. Moreover, these regimens can promote resistance, due to prolonged therapy with multiple antibiotics. A new strategy that can eradicate H. pylori as well as reduce the antibiotics used is required to prevent future antimicrobial resistance in H. pylori. Dual-therapy with vonoprazan and amoxicillin could be a breakthrough for H. pylori eradication in an era of growing antimicrobial resistance. This regimen may provide a satisfactory eradication rate of H. pylori and also minimize antimicrobial resistance due to single antibiotic use and the strong inhibitory effect of vonoprazan on gastric acid secretion.

Helicobacter pylori (H. pylori) eradication can reduce gastric cancer. However, gastric cancer still develops after eradication, and cases who received eradication therapy are increasing. In this study, we have reviewed the characteristics and predictors of primary gastric cancer developing after H. pylori eradication. In terms of the characteristics, endoscopic, histologic, and molecular characteristics are reported. Endoscopically, gastric cancer after eradication is often depressed-type and shows a gastritis-like appearance, which sometimes makes the diagnosis difficult. Histologically, most gastric cancer after eradication is intestinal type, and non-neoplastic epithelium, also called epithelium with low-grade atypia, is frequently seen over the tumor, which is presumably the cause of the endoscopic gastritis-like appearance. As for molecular characteristics, some markers, such as Ki67, MUC2, and Wnt5a expression, are lower in cancer from patients in whom H. pylori has been eradicated. In terms of predictors, several Japanese studies have reported that severe endoscopic atrophy at eradication is a risk factor for gastric cancer development. Histologic intestinal metaplasia, especially in the corpus, and long-term use of proton pump inhibitors, are also reported as risk factors for gastric cancer after H. pylori eradication. These studies on the characteristics and predictors of gastric cancer development will become the cornerstone for establishing a novel surveillance program based on the gastric cancer risk stratification specific to H. pylori-eradicated patients.

Olfactomedin-4 (OLFM4, GW112, hGC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori (H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Down-regulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advanced-stage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.

AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5 (ERCC5) and the metabolic gene glutathione S-transferase pi 1 (GSTP1) and their effects on atrophic gastritis (AG) and gastric cancer (GC) risk. METHODS Seven ERCC5 single nucleotide polymorphisms (SNPs) (rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassARRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population. RESULTS Two pairwise combinations (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk (Pinteraction = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility (Ptrend > 0.05). When the modification effect of Helicobacter pylori (H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions (ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status (Ptrend = 0.043). CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.

Due to the increasing prevalence of clarithromycin resistance, future of management of Helicobacter pylori (H. pylori) infections need to be recognized. To now, clarithromycin was the best effective, well-tolerated and safe antibiotic used in treatment of the bacterium, but, increasing trend of resistance reduced efficacy of recommended regimens. Indeed, gastroenterologists are mostly unable to start appropriate therapy-according to the sensitivity profile-due to the certain difficulties in routine H. pylori culture procedure and being time consuming method. This announcement by World Health Organization (WHO) was an onset to reconsider current challenging dilemma about H. pylori clarithromycin resistant isolates. Therefore, investigating of various factors affecting this nomination by WHO is highly welcomed. In fact, WHO enumerated more than 16 pathogens which seriously threats human life and public health, thus better management or effective guidelines are necessary. Here for the first time, we nominated this phenomenon as ‘‘gastroenterologist’s persistence’’ which should be equally investigated as antibiotic resistance. The ability of gastroenterologists to win the game against H. pylori infections is highly influenced by their collaboration with diagnostic laboratories to apply susceptibility patterns before any prescription. In conclusion, closer collaboration between two important partners (gastroenterologists and microbiologists) in management of H. pylori infection may hopefully trigger an era to remedy current crisis in clarithromycin resistance, a later gastric cancer can be practically preventable.

In their review, Arslan et al[1] did not describe the status of Helicobacter pylori (H. pylori) treatment with furazolidone and the resistance to this antibiotic. We have presented different surveys showing the resistance of H. pylori to furazolidone from Asia and South America. The resistance rates varied but were mostly low (< 5%). There are not enough data on its efficacy and resistance in the United States and Europe. H. pylori mutations occurring in the oorD gene, including A041G, A122G, C349A(G), A78G, A112G, A335G, C156T and C165T, and in the porD gene, including G353A, A356G, C357T, C347T, C347G and C346A, have been indicated to be possibly related to the observed resistance. Additionally, to complete Arslan et al's statement regarding levofloxacin resistance, it should be noted that compound mutations of N87A, A88N and V65I at codon Asn-87 were recently observed in the gyrA gene for the first time. However, the results on these topics are not sufficient, and more worldwide studies are suggested.

AIM: To investigate the relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) in an Asian population. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for observational studies published up until June 2014, without language restrictions. Additional references were obtained from reviewed articles. RESULTS: Ten studies involving 1299 IBD patients and 1817 controls were included in the meta-analysis (24.9% of IBD patients had H. pylori infection vs 48.3% of the controls). The pooled risk ratio for H. pylori infection in IBD patients compared with controls was 0.48 (95%CI: 0.43-0.54; P < 0.001). There was no significant heterogeneity in the included studies (I2 = 21%). Egger’s linear regression indicated that there was no significant publication bias (P = 0.203). CONCLUSION: The H. pylori infection rate in Asian IBD patients is significantly lower than in non-IBD patients, indicating that infection protects against the development of IBD.

A 61-year-old male from Northeast China presented with a 2-mo history of abdominal distension, pruritus and jaundice. Laboratory testing revealed an elevated serum IgG4 level. A computed tomography scan showed a typical feature of autoimmune pancreatitis (AIP) and cholecystocholangitis. Early gastric cancer was incidentally discovered when endoscopic untrasound-guided fine needle aspiration (EUS-FNA) of the pancreas was carried out. The patient underwent radical subtotal gastrectomy for gastric cancer combined with cholecystectomy. Helicobacter pylori (H. pylori) and IgG4-positive plasmacytes were detected in gastric cancer tissue, pancreatic EUS-FNA sample and resected gallbladder specimen by immunohistochemistry. The patient was diagnosed with H. pylori-positive IgG4-related AIP and sclerosing cholecystocholangitis as well as H. pylori-positive gastric cancer. He responded well to steroid therapy and remains healthy with no signs of recurrence at one year follow-up. We speculate that H. pylori might act as a trigger via direct or indirect action in the initiation of onset of gastric cancer and multiorgan IgG4-related disease.

AIM: To evaluate the role of probiotics in the standard triple Helicobacter pylori therapy. METHODS: In this meta-analysis, we investigated the efficacy of probiotics in a standard triple H. pylori therapy in adults. Searches were mainly conducted in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Fourteen studies met our criteria, and the quality of these studies was assessed using the Jadad scale. We used STATA version 12.0 to extract data and to calculate the odds ratios (ORs), which are presented with the corresponding 95% confidence intervals (CIs). The data are presented as forest plots. RESULTS: The pooled ORs for the eradication rates calculated by intention-to-treat analysis and per-protocol analysis in the probiotic group vs the control group were 1.67 (95%CI: 1.38-2.02) and 1.68 (95%CI: 1.35-2.08), respectively, using the fixed-effects model. The sensitivity of the Asian studies was greater than that of the Caucasian studies (Asian: OR = 1.78, 95%CI: 1.40-2.26; Caucasian: OR = 1.48, 95%CI: 1.06-2.05). The pooled OR for the incidence of total adverse effects was significantly lower in the probiotic group (OR = 0.49, 95%CI: 0.26-0.94), using the random effects model, with significant heterogeneity (I2 = 85.7%). The incidence of diarrhea was significantly reduced in the probiotic group (OR = 0.21, 95%CI: 0.06-0.74), whereas the incidence of taste disorders, metallic taste, vomiting, nausea, and epigastric pain did not differ significantly between the probiotic group and the control group. CONCLUSION: Supplementary probiotic preparations during standard triple H. pylori therapy may improve the eradication rate, particularly in Asian patients, and the incidence of total adverse effects.

AIM To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. METHODS In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. RESULTS We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. CONCLUSION In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier.

Aim To elucidate the epidemiological characteristics and associated risk factors of perforated peptic ulcer (PPU). Methods We retrospectively reviewed medical records of patients who were diagnosed with benign PPU from 2010 through 2015 at 6 Hallym university-affiliated hospitals. Results A total of 396 patients were identified with postoperative complication rate of 9.1% and mortality rate of 0.8%. Among 174 (43.9%) patients who were examined for Helicobacter pylori (H. pylori) infection, 78 (44.8%) patients were positive for H. pylori infection, 21 (12.1%) were on non-steroidal anti-inflammatory drugs (NSAIDs) therapy, and 80 (46%) patients were neither infected of H. pylori nor treated by any kinds of NSAIDs. Multivariate analysis indicated that older age (OR = 1.09, 95%CI: 1.04-1.16) and comorbidity (OR = 4.11, 95%CI: 1.03-16.48) were risk factors for NSAID-associated PPU compared with non-H. pylori, non-NSAID associated PPU and older age (OR = 1.04, 95%CI: 1.02-1.07) and alcohol consumption (OR = 2.08, 95%CI: 1.05-4.13) were risk factors for non-H. pylori, non-NSAID associated PPU compared with solely H. pylori positive PPU. Conclusion Elderly patients with comorbidities are associated with NSAIDs-associated PPU. Non-H. pylori, non-NSAID peptic ulcer is important etiology of PPU and alcohol consumption is associated risk factor.

Attaran et al[1] have recently shown that decreased susceptibility of established Helicobacter pylori (H. pylori) biofilms to specific antibiotics, was associated with the overtly enhanced transcription of two efflux pump genes, hp1165 and hefA, involved in specific resistance to tetracycline and multiple antibiotics, respectively. Apart from antibiotic exposure, secretion of multiple antimicrobial peptides, such as human ?-defensins (h?Ds), by the gastric epithelium upon Hp challenge, may act as early triggering events that positively impact biofilm formation and thus, antibiotic resistance. In this regard, we undertook genomic transcriptional studies using Hp 26695 strain following exposure to sublethal, similar to those present in the gastric niche, concentrations of h?Ds in an attempt to provide preliminary data regarding possible mechanisms of immune evasion and selective sensitivity of Hp. Our preliminary results indicate that h?D exposure ignites a rapid response that is largely due to the activation of several, possibly interconnected transcriptional regulatory networks - origons - that ultimately coordinate cellular processes needed to maintain homeostasis and successful adaptation of the bacterium in the gastric environment. In addition, we have shown that both antibiotic and h?D resistance are mediated by dedicated periplasmic transporters, including the aforementioned efflux pump genes hp1165 and hefA, involved in active export of antibiotics from the cell membrane and/or, as recently suggested, substrate sensing and signalling. Furthermore, it appears that sublethal doses of h?Ds may enhance biofilm formation by the sustained expression of, mainly, quorum sensing-related genes. In conclusion, we provide additional data regarding the role of specific innate immune molecules in antibiotic cross-resistance mechanisms that may deepen our understanding in the context of the development of novel eradication regimens.

Gram-negative bacteria Helicobacter pylori (H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases, diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.

Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors

Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche.

The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture- or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available culture- or molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.

AIM To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. METHODS A total of 1034 patients infected by Helicobacter pylori (H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. RESULTS Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naive patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. CONCLUSION Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

AIM To evaluate effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates from Colombia. METHODS One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cagA and vacA genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA (RAPD) fingerprinting. RESULTS Treatment effectiveness was at 74.6%. Of the participants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of post-treatment infection was 64% (16/25) and 40% (10/25) by histology and culture, respectively. Upon comparing the cagA and vacA genotypes found before and after therapy, multiple cagA genotypes (cagA-positive and cagA-negative) were found before treatment; in contrast, cagA-negative genotypes decreased after treatment. vacA s1m1 genotype was highly prevalent in patients before and after therapy. The 3’cagA region was successfully amplified in 95.5% (21/22) of the isolates obtained before and in 81.8% (18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7% (16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment. CONCLUSION Unsuccessful treatment limits colonization by low-virulence strains resulting in partial and selective eradication in mixed infections, and acts on the cagA-positive strains inducing genetic rearrangements in cagA variable region that produces a loss or gain of EPIYA repetitions.

Nearly half of the global population are carriers of Helicobacter pylori (H. pylori), a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease (PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However, the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms, but also contribute to the conversion of H. pylori into the resting (dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms, such as S-shaped, C-shaped, U-shaped, and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.

Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research.

To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods.For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P0.001; OLGIM: 83.6% vs 57.8%, P0.001).OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.

AIM: To explore the correlation between Helicobacter pylori (H. pylori)-associated gastric diseases and colorectal neoplasia. METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy (EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status (including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations. RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia (HGIEN) (OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN (5.333, 1.025-27.758) and adenocarcinoma (1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN (3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN (0.874, 0.414-1.845) and adenocarcinoma (0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN (3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN (1.481, 0.138-15.941) and adenocarcinoma (2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN (1.067, 0.264-4.314), adenoma with HGIEN (2.667, 0.231-30.800) and adenocarcinoma (2.182, 0.450-10.585) were all higher in the gastric adenocarcinoma group than in the control group. CONCLUSION: H. pylori infection as well as H. pylori-associated gastric diseases are risk factors for colorectal neoplasia.

AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning.

To determine if mir-30d inhibits the autophagy response to Helicobacter pylori (H. pylori) invasion and increases H. pylori intracellular survival.The expression of mir-30d was detected by quantitative polymerase chain reaction (PCR), and autophagy level was examined by transmission electron microscopy, western blot, and GFP-LC3 puncta assay in human AGS cells and GES-1 cells. Luciferase reporter assay was applied to confirm the specificity of mir-30d regulation on the expression of several core molecules involved in autophagy pathway. The expression of multiple core proteins were analyzed at both the mRNA and protein level, and the intracellular survival of H. pylori after different treatments was detected by gentamicin protection assay.Autophagy level was increased in AGS and GES-1 cells in response to H. pylori infection, which was accompanied by upregulation of mir-30d expression (P0.05, vs no H. pylori infection). In the two gastric epithelial cell lines, mimic mir-30d was found to repress the autophagy process, whereas mir-30d inhibitor increased autophagy response to H. pylori invasion. mir-30d mimic decreased the luciferase activity of wild type reporter plasmids carrying the 3' untranslated region (UTR) of all five tested genes (ATG2B, ATG5, ATG12, BECN1, and BNIP3L), whereas it had no effect on the mutant reporter plasmids. These five genes are core genes of autophagy pathway, and their expression was reduced significantly after mir-30d mimic transfection (P0.05, vs control cells without mir-30d mimic treatment). Mir-30d mimic transfection and direct inhibition of autophagy increased the intracellular survival of H. pylori in AGS cells.Mir-30d increases intracellular survival of H. pylori in gastric epithelial cells through inhibition of multiple core proteins in the autophagy pathway.

To compare hybrid therapy (HT) with traditional sequential therapy (ST) and concomitant therapy (CT) for Helicobacter pylori (H. pylori) eradication.We performed an electronic search of PubMed, Embase, and the CENTRAL database. Randomized controlled trials (RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol (PP) analysis (RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-to-treat (ITT) analysis (RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate (96% vs 98%, P = 0.55) and acceptable adverse event rate (30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis (RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis (RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT (95.8% vs 93.2%, P0.05). The adverse event rates of HT and CT were similar (39.5% vs 44.2%, P = 0.24).Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.

Remnant gastric cancer (RGC) and gastric stump cancer after distal gastrectomy (DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori (H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.

Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa’s cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies.

To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients.Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups.The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P0.05). All were risk factors (odds ratio1). The total symptom score of the 3 groups after treatment was lower than before treatment (P0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P0.05).FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.

We read the article "Effects of daily telephone-based re-education before taking medicine on Helicobacter pylori (H. pylori) eradication: A prospective single-center study from China" written by Wang et al with great interest. It is reported in American and European guidelines that there is no sufficient test for the diagnosis of H. pylori except culture and that using at least two different tests for diagnosis of H. pylori is recommended. Patients who used antibiotics or bismuth salts in the previous 2 wk were excluded from study. But patients who used probiotics and antioxidant vitamins such as vitamins C and E were not excluded.

To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR).The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion.The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin.The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori.

AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk. METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable self-administered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori (H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverse association between vitamin C intake and gastric cancer risk was observed for the highest (≥ 120.67 mg/d) vs the lowest (< 80.14 mg/d) intake category [OR (95%CI): 0.64 (0.46-0.88)], with a significant trend across the three intake categories (P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45 (0.32-0.63), 0.50 (0.34-0.75), 0.45 (0.25-0.81)], strawberries [0.56 (0.40-0.78), 0.49 (0.32-0.74), 0.52 (0.29-0.93)], and bananas [0.40 (0.29-0.57), 0.41 (0.27-0.62), 0.34 (0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively. CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.

To evaluate the incidence and clinical characteristics of gastric cancer (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection.Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed. Those with previous gastric ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86) and those with previous duodenal ulcer (DU) disease and H. pylori infection were assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of eradication therapy for H. pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed. Univariate and multivariate analyses were performed to identify factors influencing GC development. The relative risk of GC was evaluated using a Cox proportional hazards model.The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and 1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU-GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the HpGU-GC group than in the HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H. pylori infection were significantly associated with the development of GC (P0.05). There was no significant difference in the prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The relative risk of GC development in the HpGU-GC group compared to that of the HpDU-GC group, after correction for age and gender, was 1.71 (95%CI: 1.09-2.70; P = 0.02).GU patients with H. pylori infection had higher GC incidence rates and relative risks. Atrophy of surrounding mucosa, IM and eradication therapy were associated with GC.

AIM: To survey the detailed analyses for Helicobacter pylori (H. pylori) infection and gastric mucosal status in Myanmar. METHODS: A total of 252 volunteers with dyspeptic symptoms (155 female and 97 male; mean age of 43.6 ± 14.2 years) was participated in Yangon and Mandalay. The status of H. pylori infection was determined based on 5 different tests including rapid urease test, culture, histology, immunohistochemistry and serology. Histological scores were evaluated according to the update Sydney system and the Operative Link for Gastritis Assessment system. Pepsinogen (PG) I and PG II were measured using enzyme-linked immunosorbent assays. RESULTS: The overall prevalence of H. pylori infection was 48.0%. There was no relationship between age and infection rate. Even in young group (less than 29 years old), the H. pylori infection rate was relatively high (41.9%). The prevalence of H. pylori infection was significantly higher in Yangon than that of Mandalay. H. pylori infection was significantly associated with the presence of gastric mucosal atrophy. All 7 subjects with peptic ulcer were infected with H. pylori. Although H. pylori-positive subjects showed stronger gastritis than H. pylori-negative subjects, most cases had mild gastritis. CONCLUSION: We revealed the prevalence of H. pylori infection in patients with dyspeptic symptoms in Myanmar. The H. pylori infection was a risk factor for peptic ulcer and stronger gastritis.

To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or (13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population.The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.

To compare the Helicobacter pylori (H. pylori) eradication rate of clarithromycin-based triple therapy, metronidazole-based triple therapy, sequential therapy and concomitant therapy.A total of 680 patients infected with H. pylori were divided into 4 groups and each group was treated with a different eradication therapy. Clarithromycin-based triple therapy was applied to the first group [rabeprazole, amoxicillin and clarithromycin (PAC) group: proton pump inhibitor (PPI), amoxicillin, clarithromycin], whereas the second group was treated with metronidazole-based triple therapy [rabeprazole, amoxicillin and metronidazole (PAM) group: PPI, amoxicillin, metronidazole]. The third group was treated with rabeprazole and amoxicillin, followed by rabeprazole, clarithromycin and metronidazole (sequential group). The final group was simultaneously treated with rabeprazole, amoxicillin clarithromycin and metronidazole (concomitant therapy group). In the case of a failure to eradicate H. pylori, second-line quadruple and third-line eradication therapies were administered.The per protocol (PP) analysis was performed on 143, 139, 141 and 143 patients in the PAC, PAM, sequential and concomitant groups, respectively. We excluded patients who did not receive a C(13)-urea breath test (22, 20, 23 and 22 patients, respectively) and patients with less than an 80% compliance level (5, 11, 6 and 5 patients, respectively). The eradication rates were 76.2% (109/143) in the PAC group, 84.2% (117/139) in the PAM group, 84.4% (119/141) in the sequential group and 94.4% (135/143) in the concomitant group (P = 0.0002). All 14 patients who failed second-line therapy were treated with third-line eradication therapy. Among these 14 patients, 6 infections were successfully eradicated with the third-line therapy. Both PP and intention-to-treat analysis showed an eradication rate of 42.9% (6/14). In the PAC group, 3 of 4 patients were successfully cured (3/4, 75%); 2 of 2 patients in the PAM group (2/2, 100%) and 1 of 5 patients in the sequential group (1/5, 20%) were also cured. In the concomitant group, all 3 patients failed (0/3, 0%).The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy (ClinicalTrials.gov number NCT01922765).

Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-κB) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-κB activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status.

AIM: To quantitatively summarize and appraise the available evidence of urea breath test (UBT) use to diagnose Helicobacter pylori (H. pylori) infection in patients with dyspepsia and provide pooled diagnostic accuracy measures. METHODS: We searched MEDLINE, EMBASE, Cochrane library and other databases for studies addressing the value of UBT in the diagnosis of H. pylori infection. We included cross-sectional studies that evaluated the diagnostic accuracy of UBT in adult patients with dyspeptic symptoms. Risk of bias was assessed using QUADAS (Quality Assessment of Diagnostic Accuracy Studies)-2 tool. Diagnostic accuracy measures were pooled using the random-effects model. Subgroup analysis was conducted by UBT type (13C vs 14C) and by measurement technique (Infrared spectrometry vs Isotope Ratio Mass Spectrometry). RESULTS: Out of 1380 studies identified, only 23 met the eligibility criteria. Fourteen studies (61%) evaluated 13C UBT and 9 studies (39%) evaluated 14C UBT. There was significant variation in the type of reference standard tests used across studies.Pooled sensitivity was 0.96 (95%CI: 0.95-0.97) andpooled specificity was 0.93 (95%CI: 0.91-0.94). Likelihood ratio for a positive test was 12 and for a negative test was 0.05 with an area under thecurve of 0.985. Meta-analyses were associated with a significant statistical heterogeneity that remained unexplained after subgroup analysis. The included studies had a moderate risk of bias. CONCLUSION: UBT has high diagnostic accuracy for detecting H. pylori infection in patients with dyspepsia. The reliability of diagnostic meta-analytic estimates however is limited by significant heterogeneity.

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal metaplasia score of specimen from the greater curvature of the upper body. The type of gastritis changed from antrum-predominant gastritis to corpus-predominant gastritis with age in both populations. CONCLUSION: Gastric cancer was located in the upper part of the stomach in half of the Mongolian patients; Mongolian patients were infected with non-East-Asian-type H. pylori.

The optimal therapy for Helicobacter pylori (H. pylori) infection should combine a high cure rate and a short treatment duration with a favorable side-effect profile and should maintain a low cost. Several strategies have been proposed to increase the H. pylori eradication rate, including the extension of the treatment duration to 14 d, the use of a four-drug regimen (quadruple, sequential, and concomitant treatments), and the use of novel antibiotics, such as levofloxacin. However, triple therapy remains the most widely accepted first-line treatment regimen in Brazil and the United States and throughout Europe. Because this therapy is limited by resistance to clarithromycin, other therapeutic regimens have been investigated worldwide. This review describes the current literature involving studies directly comparing these different therapies and their efficacies.

Helicobacter cinaedi (H. cinaedi), a Gram-negative spiral-shaped bacterium, is an enterohepatic non-Helicobacter pylori Helicobacter species. We report the first case of H. cinaedi bacteremia with cellulitis after liver transplantation. A 48-year-old male, who had been a dog breeder for 15 years, underwent ABO-incompatible living-donor liver transplantation for hepatitis C virus-induced decompensated cirrhosis using an anti-hepatitis B core antibody-positive graft. The patient was preoperatively administered rituximab and underwent plasma exchange twice to overcome blood type incompatibility. After discharge, he had been doing well with immunosuppression therapy comprising cyclosporine, mycophenolate mofetil, and steroid according to the ABO-incompatible protocol of our institution. However, 7 mo after transplantation, he was admitted to our hospital with a diagnosis of recurrent cellulitis on the left lower extremity, and H. cinaedi was detected by both blood culture and polymerase chain reaction analysis. Antibiotics improved his symptoms, and he was discharged at day 30 after admission. Clinicians should be more aware of H. cinaedi in immunocompromised patients, such as ABO-incompatible transplant recipients.